A spectroscopic analysis of the interaction between the human regulatory proteins RACK1 and Ki-1/57

Biol Chem. 2006 May;387(5):577-82. doi: 10.1515/BC.2006.074.

Abstract

Ki-1/57 is a 57-kDa cytoplasmic and nuclear protein associated with protein kinase activity and is hyper-phosphorylated on Ser/Thr residues upon cellular activation. In previous studies we identified the receptor of activated kinase-1 (RACK1), a signaling adaptor protein that binds activated PKC, as a protein that interacts with Ki-1/57. Here we demonstrate that the far-UV circular dichroism spectrum of the WD repeat-containing RACK1 protein shows an unusual positive ellipticity at 229 nm, which in other proteins of the WD family has been attributed to surface tryptophans that are quenchable by N-bromosuccinimide (NBS). As well as NBS, in vitro binding of 6xHis-Ki-1/57(122-413) and 6xHis-Ki-1/57(264-413) can also quench the positive ellipticity of the RACK1 spectrum. We generated a model of RACK1 by homology modeling using a G protein beta subunit as template. Our model suggests the family-typical seven-bladed beta-propeller, with an aromatic cluster around the central tunnel that contains four Trp residues (17, 83, 150, 170), which are likely involved in the interaction with Ki-1/57.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Computer Simulation
  • GTP-Binding Protein beta Subunits / chemistry
  • GTP-Binding Protein beta Subunits / metabolism
  • Humans
  • Ki-1 Antigen / chemistry
  • Ki-1 Antigen / genetics
  • Ki-1 Antigen / metabolism*
  • Protein Binding
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism
  • Protein Kinase C beta
  • Protein Structure, Tertiary
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Spectrum Analysis / methods*
  • Two-Hybrid System Techniques

Substances

  • GTP-Binding Protein beta Subunits
  • Ki-1 Antigen
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Protein Kinase C
  • Protein Kinase C beta